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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.58 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEL
Value:
130 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
114.605 mg/m³
Explanation for the modification of the dose descriptor starting point:

There are no relevant data for repeated exposure by inhalation. The systemic NOAEL of 130 mg/kg/day from a 90 -day repeat dose oral study with rats was used for DNEL derivation. Assuming an oral /inhalation absorption of 0.5 a dose descriptor NOAEC of 114.605 mg/m3 was derived as the modified starting point. This study was used as it is a well conducted repeated dose subchronic study in rats and as it is a study of good quality (GLP, OECD guideline). For details, please see under "Additional information - Workers"

AF for dose response relationship:
1
Justification:
Based on REACH Guidance. The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
2
Justification:
Based on REACH Guidance. The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic
(end point).
AF for interspecies differences (allometric scaling):
1
Justification:
Not applicable for inhalation DNEL, per REACH Guidance. Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
AF for other interspecies differences:
2.5
Justification:
Based on REACH Guidance
AF for intraspecies differences:
5
Justification:
Based on REACH Guidance
AF for the quality of the whole database:
1
Justification:
Based on REACH Guidance
AF for remaining uncertainties:
1
Justification:
Based on REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.6 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
130 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
130 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated dermal exposure. The systemic NOAEL of 130 mg/kg/day from a 90 -day repeat dose oral study in rats was used. Assuming a dermal absorption of 50% (taking into account the physico-chemical properties), a dose descriptor of 260 mg/kg bw/d was derived

as the starting point.This study was was used for DNEL derivation as it is of good quality (GLP, OECD 408). Details can be found under "Additional information - Workers"

AF for dose response relationship:
1
Justification:
per REACH Guidance
AF for differences in duration of exposure:
2
Justification:
per REACH Guidance. Extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
4
Justification:
per REACH Guidance (allometric scaling)
AF for other interspecies differences:
2.5
Justification:
per REACH Guidance. Default value
AF for intraspecies differences:
5
Justification:
per REACH Guidance. Default value
AF for the quality of the whole database:
1
Justification:
per REACH Guidance
AF for remaining uncertainties:
1
Justification:
per REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Details of DNEL derivations for 1-naphthol

Table 1: Physchem characteristics of 1-naphthol

Parameter

 

Solid

Average aerodynamic diameter of particles

micrometer

268.252

Water solubility

g/L, in water (EpiWin)

1.11, at 20oC

Log Kow

WoE

2.84, at 22oC

Vapor Pressure

Pa (measured)

0.4, at 25oC

skin

In vivo

Irritant, Cat. 2

Eye

In vivo

Damage, Cat. 1

Skin sensitization

In vivo, LLNA (OECD 429)

Sensitizer, Cat. 1A

Acute dermal tox

in vivo

Cat 3

 NOAEL, oral, rat

Mg/kg bw/day (OECD 408)

 130

 STOT (acute inhalation)  in vivo  STOT SE-3

 

Due to the average size of the solid particles (Table 1), there is a lower potential for the substance to be respirable. Additionally, since the vapor pressure is low, exposure by inhalation is considered to be low. Although the calculated water solubility is moderate, the dry particulates first have to dissolve in the surface moisture before absorption, suggesting that the dermal absorption may be moderate. The substance is a skin irritant (Cat. 2), causes eye damage (Cat. 1) and most importantly, a skin sensitizer (Cat. 1A), and exposure can occur though dermal route. Some in vitro data on dermal absorption is available. A qualitative assessment is made for dermal exposure under the "High hazard band" category. Two long-term systemic DNELs (dermal and inhalation) are also calculated for workers.

In an OECD 408 (90-day repeated dose) study conducted under GLP conditions, male and female Crl:CD/(SD)BR VAF/Plus rats were assigned to 8 groups (15 animals/sex/group in control and exposure groups/90 days and 5 animals/sex/group in control and exposure groups/7 days). Each set of groups (1-4 and 5-8) was dosed to 0 (vehicle), 65, 130, or 400 mg/kg bw/day for 90 days. On day 7 (animals in groups 5 through 8) and once during weeks 4 and 14 (animals in groups 1 through 4), blood and urine samples were collected for hematology, clinical chemistry and urine chemistry tests. On day 7, animals in groups 5 through 8 were sacrificed and during week 14, animals in groups 1 through 4 were sacrificed, and necropsied. Microscopic examinations were done on collected tissues and sperm collected from each male was evaluated for motility, morphology, and concentration.

There was no mortality. Discolored fur (brown perineal or general yellow hair coat) was noted in femalesgiven 400 mg/kg bw/day. During Week 13, a number of treatment-related findings were noted: stained, brown hair coat in the anal- genital area of the females given 400 mg/kg/day, which was also consistent with the discolored pelage noted during the weekly clinical examinations of the high-dose females. Also, 3 high-dose males had no or low locomotor activity in the open field. A number of urine and clinical chemistry parameters were altered, however none of these findings were considered adverse. Microscopically, treatment-related changes were restricted to the stomach and spleen of animals given higher doses of 1-naphthol. In gastric tissues, squamous hyperplasia and hyperkeratosis of the non-glandular stomach were present in all males and most females given 400 mg/kg bw/day; and in both sexes at130 mg/kg bw/day. At the high-dose level, gastric changes were moderate to severe and in both sexes given 130 mg/kg bw/day were minimal to mild. In the spleen sections, increased pigment deposits (hemosiderin) were minimally to slightly increased in the 400 mg/kg bw/day group. Treatment-related stomach or changes in spleen were not observed in rats at the 65 mg/kg bw/day group.

The NOAEL for 1 -naphthol was established by the study report at 130 mg/kg bw/day, based on microscopic changes in stomach and in spleen. The local irritating effects on the rat stomach is not relevant to the human health assessment due to the anatomical difference in species (lack of nonglandular tissue in the human stomach). However, based on other findings (microscopic effects in spleen and the clinical observations) in the high dose group, the NOAEL for 1-naphthol is established at 130 mg/kg bw/day as the starting point for DNEL calculations. 

DNEL inhalation-systemic-worker for 1-naphthol:

Corrected inhalatory NOAEC: Oral NOAELx(1/sRVrat) x (ABSoral-rat/ABSinh-human)x(sRVhuman/wRV)

 

Correction for inhalation and oral absorption rates: Assume ABSoral-rat/ABSinh-human is 50/100 = 0.5

based on phys-chem properties and Endpoint Specific Guidance chapters 8 and 7c (R.7.12).

 

Conversion into an inhalatory rat NOAEC: dividing by 0.38 m3/kg (8-hour respiratory volume in the rat)

 

Correction for activity driven differences in respiratory volume in workers compared to individuals at rest: (6.7 m3/10 m3)

 

[ABS: absorption; sRV: standard Respiratory Volume; wRV: worker Respiratory Volume]

 

Corrected NOAEC = 130 mg/kg/day x (1/0.38 m3/kg/day) x (0.5) x 6.7 m3/10m3 = 114.605 mg/m3 (Dose descriptor)

                     

Applying remaining assessment factors in accordance with Endpoint Specific Guidance Chapter 8:

Correction for interspecies differences: 2.5

114.605 mg/m3/2.5 = 45.842 mg/m3

Correction for intraspecies differences: 5

45.842 mg/m3 /5 = 9.168 mg/m3

Correction for duration between subchronic to chronic: 2

9.168 mg/m3/2 = 4.584 mg/m3

Correction for dose-response:1

4.584 mg/m3/1 = 4.584 mg/m3

Correction for whole database: 1 due to quality of study

4.584 mg/m3/1 = 4.58 mg/m3

Total AF = 25

4.58 mg/m3, DNEL inhalation-systemic-worker

 

DNEL dermal-systemic-worker for 1-naphthol:

Corrections for dermal and oral absorption rates of 1-naphthol (based on Guidance on information requirements and chemical safety assessment, Chapter R 7.12): Dermal absorption is assumed to be moderate due to 1. the substance is a solid; 2. moderately soluble in water; and 3. the experimental log Kow. The substance is a skin irritant and a sensitizer to the skin. The skin absorption is assumed to be 50% (correction factor= 0.5) as actual absorption data are unavailable. The oral absorption factor is considered as100%.

Oral NOAEL (130 mg/kg/day) / 0.5 = 260 mg/kg/day = dermal dose descriptor.

Applying assessment factors in accordance with Endpoint Specific Guidance Chapter 8:

 

Correction for interspecies differences (applying allometric scaling factor of 4 for rat x 2.5 for additional factors): 10

 

260 mg/kg/day/10 = 26 mg/kg/d

Correction for intraspecies difference: 5

26 mg/kg/day/5 = 5.2 mg/kg/d

Correction for duration between sub-acute to chronic: 2

5.2 mg/kg/day/2 = 2.6 mg/kg/d

Correction for dose-response: 1 due to NOAEL

2.6 mg/kg/day/1 = 2.6 mg/kg/d

Correction for whole database: 1 due to quality of study

2.6 mg/kg/day/1 = 2.6 mg/kg/d

Total AF = 100

2.6 mg/kg/day, DNEL Dermal-worker-systemic

 

There are no consumer uses of this substance. Human exposure, via the environment, is unlikely due to the instability of the peroxide. The general population is not expected to be exposed to the substance by inhalation, dermal or oral exposures. The discharge of the substance in the environment (water, air) is extremely low. Therefore no inhalation and dermal DNELs are derived for general population. The substance is a Cat. 1 irritant to the eyes. So a qualitative approach is made for worker’s protection. Only DNELs for the relevant populations will have to be derived (Guidance on information requirements and chemical safety assessment R.8.1.2.3).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population